March 2022

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Aboobakar IF, Wiggs JL. The genetics of glaucoma: Disease associations, personalised risk assessment and therapeutic opportunities-A review. Clin Exp Ophthalmol 2022;50(2):143-162.Abstract
Glaucoma refers to a heterogenous group of disorders characterised by progressive loss of retinal ganglion cells and associated visual field loss. Both early-onset and adult-onset forms of the disease have a strong genetic component. Here, we summarise the known genetic associations for various forms of glaucoma and the possible functional roles for these genes in disease pathogenesis. We also discuss efforts to translate genetic knowledge into clinical practice, including gene-based tests for disease diagnosis and risk-stratification as well as gene-based therapies.
Amamoto R, Wallick GK, Cepko CL. Retinoic acid signaling mediates peripheral cone photoreceptor survival in a mouse model of retina degeneration. Elife 2022;11Abstract
Retinitis Pigmentosa (RP) is a progressive, debilitating visual disorder caused by mutations in a diverse set of genes. In both humans with RP and mouse models of RP, rod photoreceptor dysfunction leads to loss of night vision, and is followed by secondary cone photoreceptor dysfunction and degeneration, leading to loss of daylight color vision. A strategy to prevent secondary cone death could provide a general RP therapy to preserve daylight color vision regardless of the underlying mutation. In mouse models of RP, cones in the peripheral retina survive long-term, despite complete rod loss. The mechanism for such peripheral cone survival had not been explored. Here, we found that active retinoic acid (RA) signaling in peripheral Muller glia is necessary for the abnormally long survival of these peripheral cones. RA depletion by conditional knockout of RA synthesis enzymes, or overexpression of an RA degradation enzyme, abrogated the extended survival of peripheral cones. Conversely, constitutive activation of RA signaling in the central retina promoted long-term cone survival. These results indicate that RA signaling mediates the prolonged peripheral cone survival in the rd1 mouse model of retinal degeneration, and provide a basis for a generic strategy for cone survival in the many diseases that lead to loss of cone-mediated vision.
Andre C, Rouhana J, de Mello SS, da Cunha GR, Van Camp AG, Gilmore MS, Bispo PJM. Population structure of ocular Streptococcus pneumoniae is highly diverse and formed by lineages that escape current vaccines. Microb Genom 2022;8(3)Abstract
Streptococcus pneumoniae is a leading cause of ocular infections including serious and sight-threatening conditions. The use of pneumococcal conjugate vaccines (PCV) has substantially reduced the incidence of pneumonia and invasive pneumococcal diseases, but has had limited impact on ocular infections. Additionally, widespread vaccine use has resulted in ongoing selective pressure and serotype replacement in carriage and disease. To gain insight into the population structure of pneumococcal isolates causing ocular infections in a post-PCV-13 time period, we investigated the genomic epidemiology of ocular S. pneumoniae isolates (n=45) collected at Massachusetts Eye and Ear between 2014 and 2017. By performing a series of molecular typing methods from draft genomes, we found that the population structure of ocular S. pneumoniae is highly diverse with 27 sequence types (grouped into 18 clonal complexes) and 17 serotypes being identified. Distribution of these lineages diverged according to the site of isolation, with conjunctivitis being commonly caused by isolates grouped in the Epidemic Conjunctivitis Cluster-ECC (60 %), and ST448 (53.3 %) being most frequently identified. Conversely, S. pneumoniae keratitis cases were caused by a highly diverse population of isolates grouping within 15 different clonal complexes. Serotyping inference demonstrated that 95.5 % of the isolates were non-PCV-13 vaccine types. Most of the conjunctivitis isolates (80 %) were unencapsulated, with the remaining belonging to serotypes 15B, 3 and 23B. On the other hand, S. pneumoniae causing keratitis were predominantly encapsulated (95.2 %) with 13 different serotypes identified, mostly being non-vaccine types. Carriage of macrolide resistance genes was common in our ocular S. pneumoniae population (42.2 %), and usually associated with the mefA +msrD genotype (n=15). These genes were located in the Macrolide Efflux Genetic Assembly cassette and were associated with low-level in vitro resistance to 14- and 15-membered macrolides. Less frequently, macrolide-resistant isolates carried an ermB gene (n=4), which was co-located with the tetM gene in a Tn-916-like transposon. Our study demonstrates that the population structure of ocular S. pneumoniae is highly diverse, mainly composed by isolates that escape the PCV-13 vaccine, with patterns of tissue/niche segregation, adaptation and specialization. These findings suggest that the population structure of ocular pneumococcus may be shaped by multiple factors including PCV-13 selective pressure, microbial-related and niche-specific host-associated features.
Andres-Mateos E, Landegger LD, Unzu C, Phillips J, Lin BM, Dewyer NA, Sanmiguel J, Nicolaou F, Valero MD, Bourdeu KI, Sewell WF, Beiler RJ, McKenna MJ, Stankovic KM, Vandenberghe LH. Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate. Nat Commun 2022;13(1):1359.Abstract
Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7-14 days following injection. Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.
Anesi SD, Chang PY, Maleki A, Manhapra A, Look-Why S, Asgari S, Walsh M, Drenen K, Foster SC. Effects of Subcutaneous Repository Corticotropin Gel Injection on Regulatory T Cell Population in Noninfectious Retinal Vasculitis. Ocul Immunol Inflamm 2022;:1-10.Abstract
AIM: To evaluate the effect of repository corticotropin injection (RCI) on regulatory T cell population in patients with noninfectious retinal vasculitis. PATIENTS AND METHODS: Patients with active noninfectious retinal vasculitis were included in a prospective nonrandomized open-label study. RESULTS: Eighteen patients (33 eyes) were included in the study. Eleven (61.1%) patients [20 (60.6%) eyes] and 7 (38.9%) patients [13 (33.3%) eyes] were in the responsive and non-responsive groups, respectively. We did not find any statistically significant difference within the PPP-R group, within the PPP-NR group, or between these two groups in regard to regulatory T cell population. No significant systemic or ocular complications were found. CONCLUSION: RCI may be a complementary treatment in patients with non-infectious retinal vasculitis with or without uveitis. This study did not demonstrate an increase in regulatory T cell population in patients with noninfectious retinal vasculitis.
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Barrantes PC, Zhou P, MacDonald SM, Ioakeim-Ioannidou M, Lee NG. Granular Cell Tumor of the Orbit: Review of the Literature and a Proposed Treatment Modality. Ophthalmic Plast Reconstr Surg 2022;38(2):122-131.Abstract
PURPOSE: To document a unique case of granular cell tumor of the orbit, located lateral to and abutting the optic nerve, that benefited from treatment with proton beam irradiation, with a comprehensive review of the literature on granular cell tumor of the orbit. METHODS: Clinicopathologic case report with detailed imaging features and histopathologic and immunohistochemical evaluation for cytoplasmic tumor biomarkers differentiating granular cell tumor (GCT) from it mimicking lesions with relevant literature citations. The authors reviewed 20 cases of orbital GCT from 2011 to 2020 in addition to 40 cases from 1948 to 2011 and included a summary of imaging and clinical features, outcomes, and recommended treatment modalities. RESULTS: A 32-year-old man with 1-year history of left retrobulbar pain and diplopia on lateral gaze, intermittent left eyelid swelling, and a tonic left pupil was found to have a fusiform intraconal mass extending toward the orbital apex and abutting the optic nerve. Histopathologic and immunohistochemical investigations collectively supplied data diagnostic of a GCT with an initial low proliferation rate. GCT is a soft tissue neoplasm that originates in the nervous system and can occur anywhere in the body. This enhancing tumor is isointense to gray matter on T1-weighted MRI, hypointense on T2. After an incisional biopsy, the patient's symptoms persisted, and follow-up imaging several months later revealed further growth of the mass. The impossibility of complete surgical removal prompted the decision to treat with proton beam radiation therapy, which resulted in substantial regression in the size of the residual tumor. Most frequently involving the inferior rectus muscle (42%), orbital GCT is usually benign with only 4 reported cases of malignant orbital GCT (7%). Wide surgical resection with complete removal is usually curative for benign orbital GCT, and proton beam radiation therapy can aid in tumor shrinkage. CONCLUSIONS: GCT should be considered in the differential diagnosis when encountering patients with mass lesions involving the extraocular muscles, peripheral nerves, or less frequently, the optic nerve or orbital apex. Immunohistochemical analysis of biopsied tissue is required for the definitive diagnosis of GCT. Consideration of adjuvant therapies such as proton beam radiation therapy may be appropriate in cases of incomplete surgical resection of benign GCT. Proton beam radiation therapy can be an excellent therapeutic option for symptomatic relief and residual tumor size reduction with an acceptable toxicity profile.
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Català P, Thuret G, Skottman H, Mehta JS, Parekh M, Ní Dhubhghaill S, Collin RWJ, Nuijts RMMA, Ferrari S, LaPointe VLS, Dickman MM. Approaches for corneal endothelium regenerative medicine. Prog Retin Eye Res 2022;87:100987.Abstract
The state of the art therapy for treating corneal endothelial disease is transplantation. Advances in the reproducibility and accessibility of surgical techniques are increasing the number of corneal transplants, thereby causing a global deficit of donor corneas and leaving 12.7 million patients with addressable visual impairment. Approaches to regenerate the corneal endothelium offer a solution to the current tissue scarcity and a treatment to those in need. Methods for generating corneal endothelial cells into numbers that could address the current tissue shortage and the possible strategies used to deliver them have now become a therapeutic reality with clinical trials taking place in Japan, Singapore and Mexico. Nevertheless, there is still a long way before such therapies are approved by regulatory bodies and become clinical practice. Moreover, acellular corneal endothelial graft equivalents and certain drugs could provide a treatment option for specific disease conditions without the need of donor tissue or cells. Finally, with the emergence of gene modulation therapies to treat corneal endothelial disease, it would be possible to treat presymptomatic patients or those presenting early symptoms, drastically reducing the need for donor tissue. It is necessary to understand the most recent developments in this rapidly evolving field to know which conditions could be treated with which approach. This article provides an overview of the current and developing regenerative medicine therapies to treat corneal endothelial disease and provides the necessary guidance and understanding towards the treatment of corneal endothelial disease.
Chirapapaisan C, Muller RT, Sahin A, Cruzat A, Cavalcanti BM, Jamali A, Pavan-Langston D, Hamrah P. Effect of herpes simplex keratitis scar location on bilateral corneal nerve alterations: an in vivo confocal microscopy study. Br J Ophthalmol 2022;106(3):319-325.Abstract
AIMS: To evaluate the impact of herpes simplex virus (HSV)-induced scar location on bilateral corneal nerve alterations using laser in vivo confocal microscopy (IVCM). METHODS: Central and peripheral corneal subbasal nerve density (CSND) were assessed bilaterally in 39 patients with unilateral HSV-induced corneal scars (21 central scars (CS), 18 peripheral scars (PS)) using IVCM. Results were compared between patients and 24 age-matched controls. CSND was correlated to corneal sensation for all locations. RESULTS: Overall patients revealed significant decrease of CSND in the central and peripheral cornea (9.13±0.98 and 6.26±0.53 mm/mm2, p<0.001), compared with controls (22.60±0.77 and 9.88±0.49 mm/mm2). CS group showed a decrease in central (8.09±1.30 mm/mm2) and total peripheral nerves (5.15±0.62 mm/mm2) of the affected eyes, whereas PS group demonstrated a decrease in central (10.34±1.48 mm/mm2) and localised peripheral nerves only in the scar area (4.22±0.77 mm/mm2) (all p<0.001). In contralateral eyes, CSND decreased in the central cornea of the CS group (16.88±1.27, p=0.004), and in the peripheral area, mirroring the scar area in the affected eyes of the PS group (7.20±0.87, p=0.032). Corneal sensation significantly decreased in the whole cornea of the affected, but not in contralateral eyes (p<0.001). A positive correlation between CSND and corneal sensation was found in all locations (p<0.001). CONCLUSIONS: Patients with HSV scar demonstrate bilateral CSND decrease as shown by IVCM. CSND and corneal sensation decrease in both central and peripheral cornea in affected eyes, although only in the scar area in PS group. Interestingly, diminishment of CSND was found locally in the contralateral eyes, corresponding and mirroring the scar location in the affected eyes.
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Deffler RA, Xu J, Bittner AK, Bowers AR, Hassan SE, Ross N, Cooley S-SL, Doubt A, Davidorf FH, Dougherty BE, Dougherty BE. Use and Perceptions of Advanced Driver Assistance Systems by Older Drivers With and Without Age-Related Macular Degeneration. Transl Vis Sci Technol 2022;11(3):22.Abstract
Purpose: Advanced driver assistance systems (ADAS) have been reported to improve the safety of elderly and normally sighted drivers. The purpose of this study was to assess exposure to, perceived safety of, comfort level with, and interest in using ADAS among drivers with age-related macular degeneration (AMD). Methods: Current drivers aged 60+ years were recruited at four US sites to complete a survey about ADAS and driving habits. Frequency of use and/or perceptions of eight ADAS were investigated. An avoidance score was generated using questions about difficult driving situations. Results: The survey was completed by 166 participants (80 with AMD vs. 86 without). Participants with AMD had worse self-rated vision than those without (34% vs. 2% poor or fair rating), and drove fewer weekly miles (median [interquartile range [IQR] 30 [15 to 75] vs. 60 [30 to 121] miles, P = 0.002). Participants with AMD reported more avoidance of difficult driving situations (P < 0.001). There was no difference in the number of ADAS used by AMD status (median [IQR for AMD = 2.5 [1 to 5] vs. 3 [2 to 4] without, P = 0.87). Greater reported number of ADAS used was associated with less avoidance of difficult situations (P = 0.02). The majority perceived improved safety with most ADAS. Conclusions: Many drivers with AMD utilize common ADAS, which subjectively improve their road safety and may help to reduce self-imposed restrictions for difficult situations and mileage. Translational Relevance: Drivers with AMD are adopting readily available ADAS, for which they reported potential benefits, such as safety and less restrictive driving.
Deiner MS, Seitzman GD, Kaur G, McLeod SD, Chodosh J, Lietman TM, Porco TC. Sustained Reductions in Online Search Interest for Communicable Eye and Other Conditions During the COVID-19 Pandemic: Infodemiology Study. JMIR Infodemiology 2022;2(1):e31732.Abstract
Background: In a prior study at the start of the pandemic, we reported reduced numbers of Google searches for the term "conjunctivitis" in the United States in March and April 2020 compared with prior years. As one explanation, we conjectured that reduced information-seeking may have resulted from social distancing reducing contagious conjunctivitis cases. Here, after 1 year of continued implementation of social distancing, we asked if there have been persistent reductions in searches for "conjunctivitis," and similarly for other communicable disease terms, compared to control terms. Objective: The aim of this study was to determine if reduction in searches in the United States for terms related to conjunctivitis and other common communicable diseases occurred in the spring-winter season of the COVID-19 pandemic, and to compare this outcome to searches for terms representing noncommunicable conditions, COVID-19, and to seasonality. Methods: Weekly relative search frequency volume data from Google Trends for 68 search terms in English for the United States were obtained for the weeks of March 2011 through February 2021. Terms were classified a priori as 16 terms related to COVID-19, 29 terms representing communicable conditions, and 23 terms representing control noncommunicable conditions. To reduce bias, all analyses were performed while masked to term names, classifications, and locations. To test for the significance of changes during the pandemic, we detrended and compared postpandemic values to those expected based on prepandemic trends, per season, computing one- and two-sided P values. We then compared these P values between term groups using Wilcoxon rank-sum and Fisher exact tests to assess if non-COVID-19 terms representing communicable diseases were more likely to show significant reductions in searches in 2020-2021 than terms not representing such diseases. We also assessed any relationship between a term's seasonality and a reduced search trend for the term in 2020-2021 seasons. P values were subjected to false discovery rate correction prior to reporting. Data were then unmasked. Results: Terms representing conjunctivitis and other communicable conditions showed a sustained reduced search trend in the first 4 seasons of the 2020-2021 COVID-19 pandemic compared to prior years. In comparison, the search for noncommunicable condition terms was significantly less reduced (Wilcoxon and Fisher exact tests, P<.001; summer, autumn, winter). A significant correlation was also found between reduced search for a term in 2020-2021 and seasonality of that term (Theil-Sen, P<.001; summer, autumn, winter). Searches for COVID-19-related conditions were significantly elevated compared to those in prior years, and searches for influenza-related terms were significantly lower than those for prior years in winter 2020-2021 (P<.001). Conclusions: We demonstrate the low-cost and unbiased use of online search data to study how a wide range of conditions may be affected by large-scale interventions or events such as social distancing during the COVID-19 pandemic. Our findings support emerging clinical evidence implicating social distancing and the COVID-19 pandemic in the reduction of communicable disease and on ocular conditions.
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Gardiner SK, Kinast RM, De Moraes CG, Budenz DL, Jeoung JW, Lind JT, Myers JS, Nouri-Mahdavi K, Rhodes LA, Strouthidis NG, Chen TC, Mansberger SL. Clinicians' Use of Quantitative Information when Assessing the Rate of Functional Progression in Glaucoma. Ophthalmol Glaucoma 2022;Abstract
PURPOSE: Clinicians use both global and pointwise information from visual fields to assess the rate of glaucomatous functional progression. We asked which objective, quantitative measures best correlate with the subjective assessment by glaucoma experts. In particular, we aimed to determine how much that judgment was based on localized rates of change, versus the global indices reported by the perimeter. DESIGN: Prospective cohort study. PARTICIPANTS: Eleven academic expert glaucoma specialists independently scored the rate of functional progression from 1 (improvement) to 7 (very rapid progression), for series of 5 biannual clinical printouts from 100 glaucoma or glaucoma suspect eyes of 51 participants, 20 of which were scored twice to assess repeatability. METHODS: Regression models were used to predict the average of the 11 clinicians' scores from the objective rates of change of Mean Deviation (MD), Visual Field Index (VFI), Pattern Standard Deviation (PSD), the Nth fastest progressing location, and the Nth fastest progressing of ten anatomically-defined clusters of locations after weighting by eccentricity. MAIN OUTCOME MEASURES: The correlation between objective rates of change and the average of the 11 clinicians' scores. RESULTS: The average MD of study eyes was -2.4dB (range -16.8 to +2.8dB). The mean clinician score was highly repeatable, with intraclass correlation coefficient 0.95. It correlated better with the rate of change of VFI (pseudo-R2=0.73, 95% confidence interval [0.60, 0.83]) than MD (0.63 [0.45, 0.76]) or PSD (0.41 [0.26, 0.55]). Using pointwise information, the highest correlations were with the 5th fastest progressing location (pseudo-R2=0.71 [0.56, 0.80]), or the fastest progressing cluster after eccentricity weighting (0.61 [0.48, 0.72]). Among 25 eyes with average VFI>99%, the highest observed pseudo-R2 values was 0.34 [0.16 to 0.61] for PSD. CONCLUSIONS: Expert academic glaucoma specialists' assessment of rate of change correlated best with VFI rates, except in eyes near VFI's ceiling of 100%. Sensitivities averaged within clusters of locations have been shown to detect change sooner, but expert opinions more closely correlated to global VFI. This could be because it is currently the only index for which the perimeter automatically provides a quantitative estimate of the rate of functional progression.
Gomes PJ, Ciolino JB, Arranz P, Hernández G, Fernández N. Efficacy of once-daily ophthalmic bilastine for the treatment of allergic conjunctivitis: a dose-finding study. J Investig Allergol Clin Immunol 2022;
Gostimir M, Liou V, Yoon MK. Safety of Botulinum Toxin A Injections for Facial Rejuvenation: A Meta-Analysis of 9,669 Patients. Ophthalmic Plast Reconstr Surg 2022;Abstract
PURPOSE: To quantitatively evaluate safety profile for botulinum toxin A (BTX-A) injections among patients undergoing treatment for cosmetic indications is produced, with special attention to clinically relevant covariates and their relative impact on safety. METHODS: A systematic literature search was performed using PubMed (1996-January 2020) and Embase (1947-January 2020) to identify all randomized controlled trials (RCTs) that reported safety data for patients receiving BTX-A for cosmetic indications compared to placebo. A meta-analysis was performed to determine pooled risk ratios (RR) for treatment-related adverse events (TRAEs) and for specific adverse events. Meta-regression and additional analyses were performed for significant and/or clinically relevant covariates. RESULTS: Following the review of 8,690 studies, 32 RCTs involving 9,669 patients were included. The pooled RR of any TRAE occurring after BTX-A injection compared to placebo injection was 1.53 (95% CI, 1.33-1.77; p < 0.001). Statistically significant covariates included individual injection volume and total injection volume. The type of BTX-A formulation, treatment site, total BTX-A units, and BTX-A units per injection were not significant. Specific adverse events more likely to occur following BTX-A injection rather than placebo injection included eyelid/eyebrow malposition (RR 3.55; p < 0.001), facial paresis (RR 2.42; p = 0.316), and headache (RR 1.45; p = 0.003). Injection site reactions and injection site bruising occurred at similar rates in both groups. CONCLUSIONS: The overall safety profile of BTX-A is acceptable and consistent with previous publications. The authors' additional analyses provide a relative comparison of the impact of various treatment parameters on safety.
Guzman Aparicio MA, Chen TC. New views on three-dimensional imaging technologies for glaucoma: an overview. Curr Opin Ophthalmol 2022;33(2):103-111.Abstract
PURPOSE OF REVIEW: To summarize the literature on three-dimensional (3D) technological advances in ophthalmology, the quantitative methods associated with this, and their improved ability to help detect glaucoma disease progression. RECENT FINDINGS: Improvements in measuring glaucomatous structural changes are the result of dual innovations in optical coherence tomography (OCT) imaging technology and in associated quantitative software. SUMMARY: Compared with two-dimensional (2D) OCT parameters, newer 3D parameters provide more data and fewer artifacts.
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Heckel E, Cagnone G, Agnihotri T, Cakir B, Das A, Kim JS, Kim N, Lavoie G, Situ A, Pundir S, Sun Y, Wünnemann F, Pierce KA, Dennis C, Mitchell GA, Chemtob S, Rezende FA, Andelfinger G, Clish CB, Roux PP, Sapieha P, Smith LEH, Joyal J-S. Triglyceride-derived fatty acids reduce autophagy in a model of retinal angiomatous proliferation. JCI Insight 2022;7(6)Abstract
Dyslipidemia and autophagy have been implicated in the pathogenesis of blinding neovascular age-related macular degeneration (NV-AMD). VLDL receptor (VLDLR), expressed in photoreceptors with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acids. Since fatty acid uptake is reduced in Vldlr-/- tissues, more remain in circulation, and the retina is fuel deficient, driving the formation in mice of neovascular lesions reminiscent of retinal angiomatous proliferation (RAP), a subtype of NV-AMD. Nutrient scarcity and energy failure are classically mitigated by increasing autophagy. We found that excess circulating lipids restrained retinal autophagy, which contributed to pathological angiogenesis in the Vldlr-/- RAP model. Triglyceride-derived fatty acid sensed by free fatty acid receptor 1 (FFAR1) restricted autophagy and oxidative metabolism in photoreceptors. FFAR1 suppressed transcription factor EB (TFEB), a master regulator of autophagy and lipid metabolism. Reduced TFEB, in turn, decreased sirtuin-3 expression and mitochondrial respiration. Metabolomic signatures of mouse RAP-like retinas were consistent with a role in promoting angiogenesis. This signature was also found in human NV-AMD vitreous. Restoring photoreceptor autophagy in Vldlr-/- retinas, either pharmacologically or by deleting Ffar1, enhanced metabolic efficiency and suppressed pathological angiogenesis. Dysregulated autophagy by circulating lipids might therefore contribute to the energy failure of photoreceptors driving neovascular eye diseases, and FFAR1 may be a target for intervention.
Hunter DG. Enhancing comparison of different vision screening approaches. J AAPOS 2022;
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Ichhpujani P, Thakur S, Singh T, Singh RB, Kumar S. Effect of laser peripheral iridotomy on contrast sensitivity using Spaeth/Richman Contrast Sensitivity test. Ther Adv Ophthalmol 2022;14:25158414221078142.Abstract
Background: Laser peripheral iridotomy (LPI) is the current standard of care for primary angle-closure glaucoma. The existing literature lacks evidence regarding the effects of LPI on contrast sensitivity (CS) after the procedure. Objective: This study evaluates central and peripheral CS in patients undergoing LPI using the computer-based, Spaeth/Richman Contrast Sensitivity (SPARCS) test. Methods: We performed a pilot, prospective, interventional cohort study including 30 patients of primary angle-closure suspect (PACS) or primary angle closure (PAC) in both eyes. LPI was performed after a detailed history and clinical examination using standard procedure in all eyes. Intraocular pressure (IOP) and CS testing using SPARCS was performed before, 2 weeks and 3 months after LPI. Results: Data analyses revealed female predominance (66.67%, 20/30); the mean age of enrolled patients was 49.93 ± 10.43 years, and presenting acuity was 0.02 ± 0.06 (Log of Minimum Angle of Resolution [LogMAR]). The mean vertical cup-to-disc ratio (VCDR), mean deviation (MD in dB) and pattern standard deviation (PSD in dB) were 0.34 ± 0.09, -2.36 ± 1.72 and 2.34 ± 0.81, respectively. There was a statistically significant decrease between the pre- (15.17 ± 3.83 mmHg) and 2 weeks post-LPI (11.70 ± 1.53 mmHg) IOP (p < 0.001). However, CS in the pre- (73.47 ± 9.88) and 3 months post-LPI (75.20 ± 11.98) SPARCS scores did not reveal any statistical difference. The group-wise analysis showed a similar trend between PAC and PACS patients. Conclusion: LPI does not affect central as well as peripheral CS assessment in patients with the primary angle-closure disease.
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Lorenzo MM, Devlin J, Saini C, Cho K-S, Paschalis EI, Chen DF, Silva RNE, Chen SH, Margeta MA, Ondeck C, Solá-Del Valle D, Chodosh J, Ciolino JB, Pineda R, Pasquale LR, Shen LQ. The Prevalence of Autoimmune Diseases in Patients with Primary Open-Angle Glaucoma Undergoing Ophthalmic Surgeries. Ophthalmol Glaucoma 2022;5(2):128-136.Abstract
PURPOSE: To assess the prevalence of autoimmune disease (AiD) in patients with primary open-angle glaucoma (POAG) undergoing ophthalmic surgery. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: Patients with POAG undergoing any ophthalmic surgery and control subjects undergoing cataract surgery at the Massachusetts Eye and Ear from March 2019 to April 2020. METHODS: All available medical records with patient demographics, ocular, and medical conditions were reviewed. Differences in AiD prevalence were assessed and adjusted for covariates using multiple logistic regression. Additionally, a subgroup analysis comparing the POAG patients with and without AiD was performed. MAIN OUTCOME MEASURES: To assess the prevalence of AiD based on the American Autoimmune Related Diseases Association list. RESULTS: A total of 172 patients with POAG and 179 controls were included. The overall prevalence of AiD was 17.4% in the POAG group and 10.1% in the controls (P = 0.044); 6.4% of POAG patients and 3.4% of controls had more than 1 AiD (P = 0.18). The most prevalent AiDs in POAG group were rheumatoid arthritis (4.6%) and psoriasis (4.1%), which were also the most common in controls (2.8% each). In a fully adjusted multiple logistic regression analysis accounting for steroid use, having an AiD was associated with 2.62-fold increased odds of POAG relative to controls (95% confidence interval, 1.27-5.36, P = 0.009); other risk factors for POAG derived from the analysis included age (odds ratio [OR], 1.04, P = 0.006), diabetes mellitus (OR, 2.31, P = 0.008), and non-White ethnicity (OR, 4.75, P < 0.001). In a case-only analysis involving the eye with worse glaucoma, there was no statistical difference in visual field mean deviation or retinal nerve fiber layer (RNFL) thickness in POAG patients with AiD (n = 30) and without AiD (n = 142, P > 0.13, for both). CONCLUSIONS: A higher prevalence of AiD was found in POAG patients compared with control patients undergoing ophthalmic surgery. The presence of AiD was associated with increased risk for POAG after adjusting for covariates. Additional factors may have prevented a difference in RNFL thickness in POAG patients with and without AiD. Autoimmunity should be explored further in the pathogenesis of POAG.
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Maleki A, Look-Why S, Manhapra A, Asgari S, Garcia CM, Al-Dabbagh A, Tsang C, Chang PY, Anesi SD, Foster SC. Birdshot Chorioretinopathy: Resistant versus Responsive. Ocul Immunol Inflamm 2022;:1-6.Abstract
PURPOSE: To search findings that can explain the heterogeneity between Resistant and Responsive patients with birdshot chorioretinopathy. PATIENTS AND METHODS: This was a retrospective observational case series on "Responsive" versus "Resistant" birdshot chorioretinopathy. RESULTS: One-hundred-eighty and Ninety-nine patients were included in the Responsive and Resistant groups respectively. Multivariate analysis of paraclinical variables at the first visit demonstrated that mean deviation (p = .04), pattern standard deviation (p < .001), optic nerve head leakage (p = .012), large vessel leakage and staining (p = .01), and macular small vessel leakage (p = .03) were statistically significantly different between the two groups; however, at the visit preceding successful therapy, only macular small vessel leakage (p = .01) was statistically significantly different between the two groups. CONCLUSION: .Small vessel leakage in the macular area and/or optic nerve head leakage at the earliest visit might be risk factors for resistant birdshot chorioretinopathy.
Maleki A, Anesi SD, Look-Why S, Manhapra A, Foster SC. Pediatric uveitis: A comprehensive review. Surv Ophthalmol 2022;67(2):510-529.Abstract
Pediatric uveitis accounts for 5-10% of all uveitis. Uveitis in children differs from adult uveitis in that it is commonly asymptomatic and can become chronic and cause damage to ocular structures. The diagnosis might be delayed for multiple reasons, including the preverbal age and difficulties in examining young children. Pediatric uveitis may be infectious or noninfectious in etiology. The etiology of noninfectious uveitis is presumed to be autoimmune or autoinflammatory. The most common causes of uveitis in this age group are idiopathic and juvenile idiopathic arthritis-associated uveitis. The stepladder approach for the treatment of pediatric uveitis is based on expert opinion and algorithms proposed by multidisciplinary panels. Uveitis morbidities in pediatric patients include cataract, glaucoma, and amblyopia. Pediatric patients with uveitis should be frequently examined until remission is achieved. Once in remission, the interval between follow-up visits can be extended; however, it is recommended that even after remission the child should be seen every 8-12 weeks depending on the history of uveitis and the medications used. Close follow up is also necessary as uveitis can flare up during immunomodulatory therapy. It is crucial to measure the impact of uveitis, its treatment, and its complications on the child and the child's family. Visual acuity can be considered as an acceptable criterion for assessing visual function. Additionally, the number of cells in the anterior chamber can be a measure of disease activity. We review different aspects of pediatric uveitis. We discuss the mechanisms of noninfectious uveitis, including autoimmune and autoinflammatory etiologies, and the risks of developing uveitis in children with systemic rheumatologic diseases. We address the risk factors for developing morbidities, the Standardization of Uveitis Nomenclature (SUN) criteria for timing and anatomical classifications, and describe a stepladder approach in the treatment of pediatric uveitis based on expert opinion and algorithms proposed by multi-disciplinary panels. In this review article, We describe the most common entities for each type of anatomical classification and complications of uveitis for the pediatric population. Additionally, we address monitoring of children with uveitis and evaluation of Quality of Life.

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